PROJECT SUMMARY/ABSTRACT Disruptive behavior is one of the most common reasons for mental health referral of preschool age children and is a marker of lifetime psychiatric risk. In addition, disruptive behavior has transdiagnostic import, is often a treatment target, and is a marker of lifetime risk for mental disorder. Meta-analytic studies indicate non- psychopharmacological, family-focused therapeutic strategies as the treatment of choice in this young population. However, substantial individual differences in treatment effectiveness and the need to enhance impact during this period of early brain plasticity suggest the need for incorporating a mechanistic perspective into treatment approaches for early childhood disruptive behavior. Parent-Child Interaction Therapy (PCIT), among the most widely used empirically validated treatments for early childhood disruptive behavior, is an intervention in which a parent in coached by a clinician on discrete behavioral parenting skills during parent- child interaction. While PCIT is effective for families who complete treatment, high drop-out rates are typically reported. The primary hypothesis of this study is that improvement in parent-child dyadic synchrony, a mutually focused and reciprocated exchange between interactional partners, is a core basic mechanism for PCIT effectiveness. Our novel approach explicates this mechanism by examining neural synchrony, which assesses coherence between the signals of brain activation of parent-child dyads, and links it to the clinically-observable behavioral synchrony and clinical improvement. In a sample of 50 preschool children and their parents, we will employ functional near infrared spectroscopy (fNIRS) to measure concomitant brain activation in key regions of social cognition circuitry during an initial assessment (Visit 1), PCIT midpoint (Visit 2), PCIT completion (Visit 3), and one month follow-up (Visit 4). This proposal brings together a team of neuroscientific, developmental and intervention experts as the critical first step in translating this basic line of research to clinical application with the ultimate goals of optimizing PCIT by training clinicians to focus upon fluctuations in dyadic synchrony. We theorize that explicating bidirectional neurodevelopmental mechanisms would make PCIT (1) more effective because it would enable operating directly on a specified biological target through modification at the clinically observable level; (2) more efficient by personalizing treatment, allowing clinicians the flexibility to select from the parenting skills that most immediately alter the target on the individual level, accelerating time to clinical improvement; and (3) more generalizable as its bidirectional emphasis would facilitate the child?s capacity to read social cues and respond adaptively to social partners, which more readily translates outside the parent-child context. This study will be the first to employ neuroscientific methods to elucidate the specific mechanisms by which PCIT reduces disruptive behavior, providing a more direct and efficient clinical target. Clinical translation of findings could serve as the basis for concentrating PCIT sessions, speed the time to improvement, and reduce time commitment, thus increasing patient compliance and decreasing attrition.